Degranulation enhances release of a stable contractile factor from rabbit polymorphonuclear leukocytes.
We investigated the release of a stable contractile factor(s) from rabbit isolated polymorphonuclear leukocytes (PMNs; 10(8) cells/ml) incubated in Tyrode buffer at 37 degrees C. PMNs were untreated, stimulated with N-formylmethionyl-leucyl-phenylalanine (FMLP; 0.1 microM), of degranulated with cytochalasin B (1 microM) in combination with FMLP (0.1 microM). Products from unstimulated PMNs incubated for 60 min caused significantly greater contraction of rabbit isolated aorta (0.56 +/- 0.12 g, n = 8) than did products released from PMNs during a 5-min incubation (0.32 +/- 0.07 g, n = 11, P < 0.05). Stimulation alone did not affect contractile factor release; however, products released from degranulated PMNs caused significantly greater aortic contraction (0.48 +/- 0.08 g, n = 5) than products from nondegranulated PMNs (0.24 +/- 0.04 g, n = 5, P < 0.05) after a 5-min incubation. The contractile activity of PMN-derived products was virtually abolished by heat (90 degrees C, 10 min) or protease (trypsin; 166 U/ml, 5 h) treatment. These findings suggest a PMN-derived protein vasoconstrictor(s) is spontaneously released at a slow rate in vitro and that degranulation can enhance this rate of release. Because PMN degranulation in vivo is associated with inflammation, these results support suggestions that PMN-derived contractile factors may contribute to the impaired blood flow observed during postischemic reperfusion.
Hamilton
J R
JR
Department of Pharmacology, University of Melbourne, Parkville, Victoria, Australia.
Hart
J L
JL
Woodman
O L
OL
D000818:Animals; D001798:Blood Proteins / Q000378:metabolism*; D015550:Cell Degranulation / Q000187:drug effects; D003571:Cytochalasin B / Q000494:pharmacology; D005260:Female; D008297:Male; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D009504:Neutrophils / Q000502:physiology*; D011817:Rabbits; D014662:Vasoconstrictor Agents / Q000378:metabolism
D001798:Blood Proteins; D014662:Vasoconstrictor Agents; D003571:Cytochalasin B; D009240:N-Formylmethionine Leucyl-Phenylalanine