The chemotactic peptide receptor. A model for future understanding of chemotactic disorders.
Chemotaxis by human phagocytes enables these cells to find sites of injury or inflammation in the host. This function is a complex orchestration of biochemical and morphologic events that begins with the occupancy of specific surface receptors for chemotactic agents. The response is propagated and amplified by a biochemical cascade of transduction reactions. This cascade is mediated by receptor interactions with guanyl nucleotide binding proteins, subsequent activation of phospholipase C, and a resulting increase in phospholipid turnover. These events are spatially and temporarily integrated as elevations in the concentrations of intracellular Ca++ and diacylglycerol combine to activate protein kinase C. At the macromolecular and subcellular level, integration of these functions with as yet undiscovered pathways results in stimulation of actin polymerization, shape change, degranulation, and membrane flow. Final integration of these events results in the morphologic process of directed migration of the cell along concentration gradients of chemotaxins. During this process, chemotactic receptors are continuously regulated and feed back information to the response system that adjusts the biochemistry and morphology accordingly. This article has briefly considered some of the relationships between these transduction events and the control of a specific chemotactic receptor system employing the N-formylated chemotactic peptides. It is hoped that knowledge of this regulation will aid the physician in understanding the origin of chemotactic disorders derived from defects in chemotactic receptor systems of the phagocytic cells.
Allen
R A
RA
Department of Immunology, Research Institute of Scripps Clinic, La Jolla, California.
Traynor
A E
AE
Omann
G M
GM
Jesaitis
A J
AJ
D002118:Calcium / Q000502:physiology; D002448:Cell Adhesion; D002630:Chemotactic Factors / Q000037:antagonists & inhibitors / Q000097:blood*; D004075:Diglycerides / Q000097:blood; D006150:Guanine Nucleotides / Q000097:blood; D006801:Humans; D008055:Lipids / Q000097:blood; D009240:N-Formylmethionine Leucyl-Phenylalanine; D009504:Neutrophils / Q000378:metabolism*; D011493:Protein Kinase C / Q000097:blood; D010738:Type C Phospholipases / Q000502:physiology
D002630:Chemotactic Factors; D004075:Diglycerides; D006150:Guanine Nucleotides; D008055:Lipids; D009240:N-Formylmethionine Leucyl-Phenylalanine; D011493:Protein Kinase C; D010738:Type C Phospholipases; D002118:Calcium