Kegg Pathway: Bacterial chemotaxis - General

Microbiology. 2008 Feb; 154(Pt 2): 462-75
Bowman JP, Bittencourt CR, Ross T

High hydrostatic pressure processing (HPP) is currently being used as a treatment for certain foods to control the presence of food-borne pathogens, such as Listeria monocytogenes. Genomic microarray analysis was performed to determine the effects of HPP on L. monocytogenes in order to understand how it responds to mechanical stress injury. Reverse transcriptase PCR analysis of tufA and rpoC indicated that the reduction of mRNA expression in HPP-treated cells was dependent on intensity and time of the treatment. Treatments of 400 and 600 MPa for 5 min on cells in the exponential growth phase, though leading to partial or complete cellular inactivation, still resulted in measurable relative differential gene expression. Gene set enrichment analysis indicated that HPP induced increased expression of genes associated with DNA repair mechanisms, transcription and translation protein complexes, the septal ring, the General protein translocase system, flagella assemblage and chemotaxis, and lipid and peptidoglycan biosynthetic pathways. On the other hand, HPP appears to suppress a wide range of energy production and conversion, carbohydrate metabolism and virulence-associated genes accompanied by strong suppression of the SigB and PrfA regulons. HPP also affected genes controlled by the pleotrophic regulator CodY. HPP-induced cellular damage appears to lead to increased expression of genes linked to sections of the cell previously shown in bacteria to be damaged or altered during HPP exposure and suppression of gene expression associated with cellular growth processes and virulence.

Mol Microbiol. 2007 Dec; 66(6): 1370-81
Xu Q, Black WP, Mauriello EM, Zusman DR, Yang Z

Myxococcus xanthus requires gliding motility for swarming and fruiting body formation. It uses the Frz chemosensory pathway to regulate cell reversals. FrzCD is a cytoplasmic chemoreceptor required for sensing effectors for this pathway. NarX is a transmembrane sensor for nitrate from Escherichia coli. In this study, two NarX-FrzCD chimeras were constructed to investigate M. xanthus chemotaxis: NazD(F) contains the N-terminal sensory module of NarX fused to the C-terminal signalling domain of FrzCD; NazD(R) is similar except that it contains a G51R mutation in the NarX domain known to reverse the signalling output of a NarX-Tar chimera to nitrate. We report that while nitrate had no effect on the wild type, it decreased the reversal frequency of M. xanthus expressing NazD(F) and increased that of M. xanthus expressing NazD(R). These results show that directional motility in M. xanthus can be regulated independently of cellular metabolism and physiology. Surprisingly, the NazD(R) strain failed to adapt to nitrate in temporal assays as did the wild type to known repellents. The lack of temporal adaptation to negative stimuli appears to be a General feature in M. xanthus chemotaxis. Thus, the appearance of biased movements by M. xanthus in repellent gradients is likely due to the inhibition of net translocation by repellents.

J Cell Biol. 2007 Oct 8; 179(1): 33-40
Palumbo R, Galvez BG, Pusterla T, De Marchis F, Cossu G, Marcu KB, Bianchi ME

Tissue damage is usually followed by healing, as both differentiated and stem cells migrate to replace dead or damaged cells. Mesoangioblasts (vessel-associated stem cells that can repair muscles) and fibroblasts migrate toward soluble factors released by damaged tissue. Two such factors are high mobility group box 1 (HMGB1), a nuclear protein that is released by cells undergoing unscheduled death (necrosis) but not by apoptotic cells, and stromal derived factor (SDF)-1/CXCL12. We find that HMGB1 activates the canonical nuclear factor kappaB (NF-kappaB) pathway via extracellular signal-regulated kinase phosphorylation. NF-kappaB signaling is necessary for chemotaxis toward HMGB1 and SDF-1/CXCL12, but not toward growth factor platelet-derived growth factor, formyl-met-leu-phe (a peptide that mimics Bacterial invasion), or the archetypal NF-kappaB-activating signal tumor necrosis factor alpha. In dystrophic mice, mesoangioblasts injected into the General circulation ingress inefficiently into muscles if their NF-kappaB signaling pathway is disabled. These findings suggest that NF-kappaB signaling controls tissue regeneration in addition to early events in inflammation.

Math Biosci Eng. 2007 Apr; 4(2): 187-203
Chiu C, Yu JL

Reaction-diffusion-chemotaxis systems have proven to be fairly accurate mathematical models for many pattern formation problems in chemistry and biology. These systems are important for computer simulations of patterns, parameter estimations as well as analysis of the biological systems. To solve reaction-diffusion-chemotaxis systems, efficient and reliable numerical algorithms are essential for pattern generations. In this paper, a General reaction-diffusion-chemotaxis system is considered for specific numerical issues of pattern simulations. We propose a fully explicit discretization combined with a variable optimal time step strategy for solving the reaction-diffusion-chemotaxis system. Theorems about stability and convergence of the algorithm are given to show that the algorithm is highly stable and efficient. Numerical experiment results on a model problem are given for comparison with other numerical methods. Simulations on two real biological experiments will also be shown.

J Am Chem Soc. 2007 Aug 22; 129(33): 10261-8
Ma L, Cui Q

Advanced computational techniques including transition path sampling and free energy calculations are combined synergistically to reveal the activation mechanism at unprecedented resolution for a small signaling protein, chemotaxis protein Y. In the conventional "Y-T coupling" model for response regulators, phosphorylation induces the displacement of the conserved Thr87 residue through hydrogen-bond formation, which in turn makes it sterically possible for Tyr106 to isomerize from a solvent exposed configuration to a buried rotameric state. More than 160 unbiased activation trajectories show, however, that the rotation of Tyr106 does not rely on the displacement of Thr87 per se. Free energy calculations reveal that the Tyr106 rotation is a low-barrier process in the absence of the Thr87-phosphate hydrogen bond, although the rotation is stabilized by the formation of this interaction. The simulations also find that structural change in the beta4-alpha4 loop does not gate the Tyr106 rotation as suggested previously; rather, the rotation of Tyr106 stabilizes the activated configuration of this loop. The computational strategy used and mechanistic insights obtained have an impact on the study of signaling proteins and allosteric systems in General.

Methods Enzymol. 2007; 423: 392-413
Porter SL, Wadhams GH, Armitage JP

This chapter describes both the in vivo and in vitro methods that have been successfully used to analyze the chemotaxis pathways of R. sphaeroides, showing that two operons each encode a complete chemosensory pathway with each forming into independent signaling clusters. The methods used range from in vitro analysis of the chemotaxis phosphorylation reactions to protein localization experiments. In vitro analysis using purified proteins shows a complex pattern of phosphotransfer. However, protein localization studies show that the R. sphaeroides chemotaxis proteins are organized into two distinct sensory clusters -- one containing transmembrane receptors located at the cell poles and the other containing soluble chemoreceptors located in the cytoplasm. Signal outputs from both clusters are essential for chemotaxis. Each cluster has a dedicated chemotaxis histidine protein kinase (HPK), CheA. There are a total of eight chemotaxis response regulators in R. sphaeroides, six CheYs and two CheBs, and each CheA shows a different pattern of phosphotransfer to these response regulators. The spatial separation of homologous proteins may mean that reactions that happen in vitro do not occur in vivo, suggesting great care should be taken when extrapolating from purely in vitro data to cell physiology. The methods described in this chapter are not confined to the study of R. sphaeroides chemotaxis but are applicable to the study of complex two-component systems in General.

FEBS J. 2007 Jul; 274(14): 3513-8
McCormick BA

Bacterial infections at epithelial surfaces, such as those that line the gut and the lung, stimulate the migration of neutrophils through the co-ordinated actions of chemoattractants secreted from pathogen-stimulated epithelial cells. One such factor involved in attracting polymorphonuclear leukocytes across the epithelium and into the lumen has until recently remained elusive. In 2004, we identified the eicosanoid, hepoxilin A(3), to be selectively secreted from the apical surface of human intestinal or lung epithelial cells stimulated with Salmonella enterica serotype Typhimurium or Pseudomonas aeruginosa, respectively. In this role, the function of hepoxilin A(3) is to guide neutrophils, via the establishment of a gradient, across the epithelial tight junction complex. Interestingly, interruption of the synthetic pathway of hepoxilin A(3) blocks the apical release of hepoxilin A(3)in vitro and the transmigration of neutrophils induced by S. typhimurium both in in vitro and in vivo models of inflammation. Such results have led to the discovery of a completely novel pathway that is not only critical for responses to Bacterial pathogens but also has broad implications for inflammatory responses affecting mucosal surfaces in General. Thus, the objective of this review was to highlight the recent findings that implicate hepoxilin A(3) as a key regulator of mucosal inflammation.

Appl Microbiol Biotechnol. 2007 Aug; 76(2): 447-57
Zhang W, Culley DE, Nie L, Scholten JC

Biofilm build-up of sulphate-reducing bacteria (SRB) on metal surfaces may lead to severe corrosion of iron. To understand the processes at molecular level, in this study, a whole-genome oligonucleotide microarray was used to examine differential expression patterns between planktonic populations and mature biofilm of Desulfovibrio vulgaris on a steel surface. Statistical analysis revealed that 472 genes were differentially expressed (1.5-fold or more with a q value less than 0.025) by comparing the biofilm cells with the planktonic cells. Among the differentially expressed genes were several that corresponded to genes identified in many aerobic Bacterial biofilms (i.e., Pseudomonas species and Escherichia coli) such as genes encoding flagellin, a flagellar motor switch protein, chemotaxis proteins involved in cell motility, as well as genes involved in exopolysaccharide biosynthesis. In addition, the biofilm-bound cells of D. vulgaris exhibited decreased transcription of genes involved in protein synthesis, energy metabolism and sulfate reduction, as well as genes involved in General stress responses. These findings were all consistent with early suggestion that the average physiology of the biofilm cells were similar to cells reduced in growth. Most notably, up-regulation of large number of outer membrane proteins was observed in the D. vulgaris biofilm. Although their function is still unknown, the higher expression of these genes in the biofilm could implicate important roles in the formation and maintenance of multi-cellular consortium on a steel surface. The study provided insights into the metabolic networks associated with the formation and maintenance of a D. vulgaris biofilm on a steel surface.

J Bacteriol. 2007 Aug; 189(15): 5523-33
Lane MC, Simms AN, Mobley HL

Type 1 fimbriae and flagella have been previously shown to contribute to the virulence of uropathogenic Escherichia coli (UPEC) within the urinary tract. In this study, the relationship between motility and type 1 fimbrial expression was tested for UPEC strain CFT073 by examining the phenotypic effect of fimbrial expression on motility and the effect that induction of motility has on type 1 fimbrial expression. While constitutive expression of type 1 fimbriae resulted in a significant decrease in motility and flagellin expression (P < 0.0001), a loss of type 1 fimbrial expression did not result in increased motility. Additionally, hypermotility and flagellar gene over- and underexpression were not observed to affect the expression of type 1 fimbriae. Hence, it appeared that the relationship between type 1 fimbrial expression and motility is unidirectional, where the overexpression of type 1 fimbriae dramatically affects motility and flagellum expression but not vice versa. Moreover, the constitutive expression of type 1 fimbriae in UPEC cystitis isolate F11 and the laboratory strain E. coli K-12 MG1655 also resulted in decreased motility, suggesting that this phenomenon is not specific to CFT073 or UPEC in General. Lastly, by analyzing the repression of motility caused by constitutive type 1 fimbrial expression, it was concluded that the synthesis and presence of type 1 fimbriae at the Bacterial surface is only partially responsible for the repression of motility, as evidenced by the partial restoration of motility in the CFT073 fim L-ON DeltafimAICDFGH mutant. Altogether, these data provide further insight into the complex interplay between type 1 fimbrial expression and flagellum-mediated motility.

FEMS Immunol Med Microbiol. 2007 Jul; 50(2): 257-63
Cróinín TO, McCormack A, van Vliet AH, Kusters JG, Bourke B

Helicobacter mustelae is a gastric pathogen of ferrets, where it causes disorders similar to those caused by Helicobacter pylori in humans. The H. mustelae ferret model therefore has potential for the in vivo study of Helicobacter pathogenesis in General. In this study a library of 500 individual H. mustelae mutants was generated using an in vitro random insertion mutagenesis technique. Mutants were subsequently tested for motility and adherence, and 43 of the 500 mutants tested were found to be nonmotile in a soft agar assay. Of these 43 mutants, seven were subsequently identified as deficient in their ability to adhere to AGS cells. Insertion had taken place in different positions in the H. mustelae genome, and included mutants in or near to genes involved in motility and urease activity (e.g. the chemotaxis gene cheV and the urease accessory gene ureH). The development of a mutant library for a natural animal model of Helicobacter infection provides the opportunity to study in vivo the role of candidate Helicobacter virulence genes.

J Gen Physiol. 2007 Feb; 129(2): 95-100
Palmer LG

Syst Biol (Stevenage). 2004 Dec; 1(2): 222-9
Lebiedz D, Maurer H

Detailed quantitative understanding and specific external control of cellular behaviour are General long-term goals of modem bioscience research activities in systems biology. Pattern formation and self-organisation processes both in single cells and in distributed cell populations are phenomena which are highly significant for the functionality of life, because life requires to maintain a highly organised spatiotemporal system structure. In particular chemotaxis is crucial for various biological aspects of intercellular signalling and cell aggregation. As an example for model based control of self-organising biological systems, we describe numerical optimal control of E. coli Bacterial chemotaxis based on a 1-D two-component partial differential equation (PDE) model of reaction diffusion type. We present a numerical scheme to force cell aggregation patterns to particular desired results by applying a boundary influx control of chemoattractant without interfering with the system itself. Optimal controls are numerically computed by using a specially tailored interior point optimisation technique applied to a direct collocation discretisation of the control function and the PDE constraint. The objective to be minimised is the deviation of a desired cell distribution from the cell density, which results from the dynamics of the controlled system.

Appl Environ Microbiol. 2006 Sep; 72(9): 6331-44
Chourey K, Thompson MR, Morrell-Falvey J, Verberkmoes NC, Brown SD, Shah M, Zhou J, Doktycz M, Hettich RL, Thompson DK

The biological impact of 24-h ("chronic") chromium(VI) [Cr(VI) or chromate] exposure on Shewanella oneidensis MR-1 was assessed by analyzing cellular morphology as well as genome-wide differential gene and protein expression profiles. Cells challenged aerobically with an initial chromate concentration of 0.3 mM in complex growth medium were compared to untreated control cells grown in the absence of chromate. At the 24-h time point at which cells were harvested for transcriptome and proteome analyses, no residual Cr(VI) was detected in the culture supernatant, thus suggesting the complete uptake and/or reduction of this metal by cells. In contrast to the untreated control cells, Cr(VI)-exposed cells formed apparently aseptate, nonmotile filaments that tended to aggregate. Transcriptome profiling and mass spectrometry-based proteomic characterization revealed that the principal molecular response to 24-h Cr(VI) exposure was the induction of prophage-related genes and their encoded products as well as a number of functionally undefined hypothetical genes that were located within the integrated phage regions of the MR-1 genome. In addition, genes with annotated functions in DNA metabolism, cell division, biosynthesis and degradation of the murein (peptidoglycan) sacculus, membrane response, and General environmental stress protection were upregulated, while genes encoding chemotaxis, motility, and transport/binding proteins were largely repressed under conditions of 24-h chromate treatment.

J Biol Chem. 2006 Oct 13; 281(41): 30512-23
Asinas AE, Weis RM

In Bacterial chemotaxis, clustered transmembrane receptors and the adaptor protein CheW regulate the kinase CheA. Receptors outnumber CheA, yet it is poorly understood how interactions among receptors contribute to regulation. To address this problem, receptor clusters were simulated using liposomes decorated with the cytoplasmic domains of receptors, which supported CheA binding and stimulation. Competitive and cooperative interactions were revealed through the use of known receptor signaling mutants, which were used in mixtures with the wild type domain. Competitive effects among the receptor domains sorted cleanly into two categories defined by either stronger or weaker interactions with CheA. Cooperative effects were also evident in CheA binding and activity. In the transition from the stimulating to the inhibiting states, both the cooperativity of the transition and the persistence of stimulation by the wild type domain increased with receptor modification, as in the intact receptor. We conclude that competitive and cooperative receptor interactions both contribute to CheA regulation and that liposome-mediated assembly is effective in addressing these General membrane phenomena.

Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2006 May; 101(5): 681-6
Iwama A, Morimoto T, Tsuji M, Nakamura K, Higuchi N, Imaizumi I, Shibata N, Yamasaki M, Nakamura H

OBJECTIVE: The purpose of this study was to investigate the relationship between type 2 diabetes mellitus and anaerobic bacteria detected in infected root canals. STUDY DESIGN: Normal Wistar rats (control) received a standard laboratory diet with water (group A), and GK rats (type 2 diabetes mellitus rats) a normal laboratory diet with water (group B) or a 30% sucrose solution (group C). chemotaxis assay was conducted on polymorphonuclear leukocytes from the 3 groups, and the numbers of anaerobic bacteria in infected root canals were determined. RESULTS: In the chemotaxis assay on the polymorphonuclear leukocytes, the chemotactic response of cells in group C was lower than that for groups A and B (P < .01). As to bacteria detected in the root canal, obligate anaerobic bacteria which stained gram negative, were significantly more numerous in group C (P < .01) than in groups A and B. CONCLUSION: The metabolic condition produced by type 2 diabetes mellitus in rats might lower the General host resistance against Bacterial infection.

Microbiology. 2006 Mar; 152(Pt 3): 831-53
Budde I, Steil L, Scharf C, Völker U, Bremer E

The soil bacterium Bacillus subtilis frequently encounters a reduction in temperature in its natural habitats. Here, a combined transcriptomic and proteomic approach has been used to analyse the adaptational responses of B. subtilis to low temperature. Propagation of B. subtilis in minimal medium at 15 degrees C triggered the induction of 279 genes and the repression of 301 genes in comparison to cells grown at 37 degrees C. The analysis thus revealed profound adjustments in the overall gene expression profile in chill-adapted cells. Important transcriptional changes in low-temperature-grown cells comprise the induction of the SigB-controlled General stress regulon, the induction of parts of the early sporulation regulons (SigF, SigE and SigG) and the induction of a regulatory circuit (RapA/PhrA and Opp) that is involved in the fine-tuning of the phosphorylation status of the Spo0A response regulator. The analysis of chill-stress-repressed genes revealed reductions in major catabolic (glycolysis, oxidative phosphorylation, ATP synthesis) and anabolic routes (biosynthesis of purines, pyrimidines, haem and fatty acids) that likely reflect the slower growth rates at low temperature. Low-temperature repression of part of the SigW regulon and of many genes with predicted functions in chemotaxis and motility was also noted. The proteome analysis of chill-adapted cells indicates a major contribution of post-transcriptional regulation phenomena in adaptation to low temperature. Comparative analysis of the previously reported transcriptional responses of cold-shocked B. subtilis cells with this data revealed that cold shock and growth in the cold constitute physiologically distinct phases of the adaptation of B. subtilis to low temperature.

J Biol Chem. 2006 Mar 17; 281(11): 7189-96
Christmas P, Tolentino K, Primo V, Berry KZ, Murphy RC, Chen M, Lee DM, Soberman RJ

Leukotriene B(4) (LTB(4)) is a potent chemoattractant for polymorphonuclear leukocytes (PMN) and other cells. Human PMN inactivate LTB(4) by omega-oxidation catalyzed by cytochrome P-450 (CYP) 4F3A. The contribution of the enzymatic inactivation of LTB(4) by CYP4Fs to down-regulating functional responses of cells to LTB(4) is unknown. To elucidate the role of CYP4F-mediated inactivation of LTB(4) in terminating the responses of PMN to LTB(4) and to identify a target for future genetic studies in mice, we have identified the enzyme that catalyzes the omega-1 and omega-2 oxidation of LTB(4) in mouse myeloid cells as CYP4F18. As determined by mass spectrometry, this enzyme catalyzes the conversion of LTB(4) to 19-OH LTB(4) and to a lesser extent 18-OH LTB(4). Inhibition of CYP4F18 resulted in a marked increase in calcium flux and a 220% increase in the chemotactic response of mouse PMN to LTB(4). CYP4F18 expression was induced in bone marrow-derived dendritic cells by Bacterial lipopolysaccharide, a ligand for TLR4, and by poly(I.C), a ligand for TLR3. However, when bone marrow-derived myeloid dendritic cells trafficked to popliteal lymph nodes from paw pads, the expression of CYP4F18 was down-regulated. The results identify CYP4F18 as a critical protein in the regulation of LTB(4) metabolism and functional responses in mouse PMN and identify it as the functional orthologue of human PMN CYP4F3A.

J Bacteriol. 2005 Nov; 187(22): 7840-4
Bardy SL, Maddock JR

A soluble methyl-accepting chemotaxis protein (MCP) of Pseudomonas aeruginosa, McpS, showed polar localization by immunofluorescence microscopy. Overexpression of McpS resulted in a dominant-negative effect on chemotaxis and caused a loss of polar clustering of the General MCP population. The polar localization of a soluble MCP defines a third, and unexpected, paradigm for cellular MCP localization.

Biotechnol Bioeng. 2005 Nov 5; 92(3): 277-98
Jürgen B, Tobisch S, Wümpelmann M, Gördes D, Koch A, Thurow K, Albrecht D, Hecker M, Schweder T

A detailed gene expression analysis of industrial-close Bacillus subtilis fed-batch fermentation processes with casamino acids as the only nitrogen source and with a reduced casamino acid concentration but supplemented by ammonia was carried out. Although glutamine and arginine are supposed to be the preferred nitrogen sources of B. subtilis, we demonstrate that a combined feeding of ammonia and casamino acids supports cell growth under fed-batch fermentation conditions. The transcriptome and proteome analyses revealed that the additional feeding of ammonia in combination with a reduced amino acid concentration results in a significantly lower expression level of the glnAR or tnrA genes, coding for proteins, which are mainly involved in the nitrogen metabolism of B. subtilis. However, the mRNA levels of the genes of the ilvBHC-leuABD and hom-thrCB operons were significantly increased, indicating a valine, leucine, isoleucine, and threonine limitation under these fermentation conditions. In contrast, during the fermentation with casamino acids as the only nitrogen source, several genes, which play a crucial role in nitrogen metabolism of B. subtilis (e.g., glnAR, nasCDE, nrgAB, and ureABC), were up-regulated, indicating a nitrogen limitation under these conditions. Furthermore, increased expression of genes, which are involved in motility and chemotaxis (e.g., hag, fliT) and in acetoin metabolism (e.g., acoABCL), was determined during the fermentation with the mixed nitrogen source of casamino acids and ammonia, indicating a carbon limitation under these fermentation conditions. Under high cell density and slow growth rate conditions a weak up-regulation of autolysis genes could be observed as well as the induction of a number of genes involved in motility, chemotaxis and General stress response. Results of this study allowed the selection of marker genes, which could be used for the monitoring of B. subtilis fermentation processes. The data suggest for example acoA as a marker gene for glucose limitation or glnA as an indicator for nitrogen limitation.

Med Sci Sports Exerc. 2005 Jun; 37(6): 949-54
Wolach B, Gavrieli R, Ben-Dror SG, Zigel L, Eliakim A, Falk B

PURPOSE: Intense exercise affects the immune system, increasing the susceptibility of athletes to viral and Bacterial infections. We have previously shown a significant decrease of fMLP-neutrophil migration 24 h after aerobic exercise. In this study we aimed to look at the differential effect of different chemoattractants on neutrophil migration following aerobic exercise, to determine the recovery time, and to better understand the role of the cell skeleton behind the impaired chemotaxis. METHODS: Sixteen female volunteers aged 22-30 yr were tested before, 24, and 48 h after aerobic exercise (30 min running at 70% (.)VO(2max). The submaximal exercise test was conducted a week after the (.)VO(2max) test.We studied the membrane cell receptor response to fMLP, IL-8, and C5a, which have specific ligand-receptor pathways. Further, we studied the cytoskeletal response by investigating the cell polarization and the F-actin polymerization. RESULTS: Significant decrease of the neutrophil net chemotaxis was detected with fMLP, IL-8 and C5a, 24 h after exercise (50 +/- 5%, P = 0.0001; 48 +/- 12%, P = 0.0015; and 32 +/- 11%, P = 0.011, respectively). Complete recovery was observed within 48 h with all chemoattractants. Normal neutrophil random migration and F-actin polymerization were found. Decreased neutrophil polarization was detected (46 +/- 6% vs 22 +/- 8% of polarized cells, before and after effort, respectively; P = 0.004). Correlation between polarization and chemotactic migration was found (r = 0.945; P = 0.001). CONCLUSIONS: The impaired chemotactic response, observed 24 h after exercise, was similar using different chemoattractants. This finding indicates a possible exercise-induced effect on a common factor at the ligand-receptor level. The abnormal cell polarization indicates skeletal dysfunction that should be further investigated and elucidated. The normal fMLP-stimulated-F-actin polymerization reflects an adequate pathway of signal transduction for the formyl peptide.