title: Modulating influence of chemotactic factor-induced cell adhesiveness on granulocyte function.
abstract: 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.
mesh_terms: 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
chemical_list: D001786:Blood Glucose; D005561:Formates; D006600:Hexosephosphates; D009842:Oligopeptides