Modulating influence of chemotactic factor-induced cell adhesiveness on granulocyte function.
The importance of adhesion in regulating locomotion and accumulation of polymorphonuclear leukocytes (PMN) has remained vague. We found that the chemotaxis of human PMN resuspended in heat-inactivated plasma was maximal toward 1-10 nM N-formyl-met-leu-phe (f-Met-Leu-Phe), but fell below random motility toward >/= 100 nM. This impressive decrease of motility was paralleled by increased cell adherence on Petri dishes being minimal at 1 nM and maximal at >10 nM f-Met-Leu-Phe (6+/-1 and 37+/-2% [SE] adherent cells, respectively). Checked by phase-contrast microscopy, cells under stimulated adhesion lost the typical bipolar shape of moving PMN and became immobilized and highly flattened. PMN, preexposed to 250 nM f-Met-Leu-Phe and tested after washing, retained increased adhesiveness and showed extremely low random and chemotactic motility. In contrast, preexposure to 1 nM f-Met-Leu-Phe had no effect on chemotaxis. Supporting the concept that immobilizing hyperadhesiveness does not correspond to a general functional hyporesponsiveness of PMN, no depression of the initial ingestion rate was observed in the presence of 250 nM f-Met-Leu-Phe. Moreover, a close correlation was found between the induction of PMN adhesiveness and the stimulation of the hexose monophosphate pathway activity as well as of lysomal enzyme release (r >/= 0.98). Thus, "chemotactic deactivation" and "high-dose inhibition of chemotaxis" by N-formyl peptides is the consequence of increased cell adhesiveness. This phenomenon provides a mechanism for cell trapping at the inflammatory site. Conversely, if operative in circulating blood, e.g., in septicemia, it may impair PMN emigration to such sites.
D000328:Adult; D001786:Blood Glucose / Q000378:metabolism; D002448:Cell Adhesion / Q000187:drug effects; D002634:Chemotaxis, Leukocyte / Q000187:drug effects; D005561:Formates / Q000494:pharmacology; D006600:Hexosephosphates / Q000097:blood; D006801:Humans; D066298:In Vitro Techniques; D008247:Lysosomes / Q000187:drug effects / Q000201:enzymology; D009504:Neutrophils / Q000166:cytology / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D009842:Oligopeptides / Q000494:pharmacology; D010084:Oxidation-Reduction; D010587:Phagocytosis / Q000187:drug effects
D001786:Blood Glucose; D005561:Formates; D006600:Hexosephosphates; D009842:Oligopeptides