Inhibition of neutrophil functions by platelets and platelet-derived products: description of multiple inhibitory properties.
The effect of platelets and their products on in vitro responses of human neutrophils to f-met-leu-phe (fMLP) and phorbol myristate acetate (PMA) was studied. Platelets produced a concentration-dependent inhibition of neutrophil superoxide anion (O2-) generation with maximum inhibition of the response to fMLP approaching 42.2 +/- 5.4% and that to PMA approaching 85.9 +/- 3.4%. Supernates of thrombin-activated platelets produced maximal inhibition of neutrophil O2- generation in response to fMLP (66.3 +/- 4.2%) at a ratio of 10 platelet equivalents (PEQ) to 1 neutrophil but failed to affect the cells' response to PMA. In contrast, lysate of sonicated platelets inhibited neutrophil O2- generation in response to both fMLP (59.6 +/- 2.0%) and PMA (90.1 +/- 1.3%). Biochemical characterization of platelet lysate identified at least two stimulus-specific inhibitory activities which differ in size, thermal stability and enzyme sensitivity. Platelet lysate also maximally inhibited neutrophil degranulation and chemotaxis at a ratio of 20 PEQ to 1 neutrophil. Our findings indicate that physiologically achievable levels of platelets or their products modulate the response of neutrophils in a stimulus-specific manner and are thereby capable of potentially limiting tissue damage which accompanies neutrophil activation during inflammation.
McGarrity
S T
ST
Department of Internal Medicine, St. Louis University School of Medicine, Missouri 63104.
Hyers
T M
TM
Webster
R O
RO
D000893:Anti-Inflammatory Agents / Q000378:metabolism / Q000502:physiology; D001792:Blood Platelets / Q000378:metabolism / Q000502:physiology*; D002458:Cell Fractionation; D002474:Cell-Free System; D002634:Chemotaxis, Leukocyte / Q000187:drug effects; D003594:Cytoplasmic Granules / Q000201:enzymology; D006801:Humans; D008247:Lysosomes / Q000201:enzymology; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D009504:Neutrophils / Q000201:enzymology / Q000276:immunology / Q000502:physiology*; D013481:Superoxides / Q000037:antagonists & inhibitors; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D000893:Anti-Inflammatory Agents; D013481:Superoxides; D009240:N-Formylmethionine Leucyl-Phenylalanine; D013755:Tetradecanoylphorbol Acetate