DEGRANULATION ENHANCES RELEASE OF A STABLE CONTRACTILE FACTOR FROM RABBIT POLYMORPHONUCLEAR LEUKOCYTES

We investigated the release of a stable contractile factor(s) from rab bit isolated polymorphonuclear leukocytes (PMNs; 10(8) cells/ml) incub ated in Tyrode buffer at 37 degrees C. PMNs were untreated, stimulated with N-formylmethionylleucyl-phenylalanine (FMLP; 0.1 mu M), or degra nulated with cytochalasin B (1 mu M) in combination with FMLP (0.1 mu M). Products from unstimulated PMNs incubated for 60 min caused signif icantly 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 degranula ted PMNs caused significantly greater aortic contraction (0.48 +/- 0.0 8 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, 1 0 min) or protease (trypsin; 166 U/ml, 5 h) treatment. These findings suggest a PMN-derived protein vasoconstrictor(s) is spontaneously rele ased at a slow rate in vitro and that degranulation can enhance this r ate of release. Because PMN degranulation in vivo is associated with i nflammation, these results support suggestions that PMN-derived contra ctile factors may contribute to the impaired blood flow observed durin g postischemic reperfusion.