Plasma activation of neutrophil cd18 after skeletal muscle ischemia
- a potential mechanism for late systemic injury.
Petrasek, Paul F., Thomas F. Lindsay, Alexander D. Romaschin, and Paul
M. Walker.
R. Fraser Elliot Vascular Surgery Research Laboratory, The Toronto
Hospital, University of Toronto, Ontario, Canada, M5G 2C4
APStracts 2:0446H, 1995.
Reperfusion of acutely ischemic skeletal muscle is associated with
neutrophil activation which may augment local injury or cause damage
to distant organs. Neutrophil (PMN) glycoprotein CD18 plays a role in
this injury, since its blockade substantially reduces damage, however
its mechanisms of control during reperfusion are poorly understood.
The purpose of this study was to investigate the importance of
circulating plasma factors to CD18-dependent neutrophil function
during reperfusion and to relate these to quantitative expression of
CD18. Eight rabbits were subject to hindlimb ischemia for 5 hours,
followed by 48 hours reperfusion. Plasma collected at seven intervals
was incubated with unstimulated PMNs from uninjured rabbits. CD18
-specific neutrophil activation was evaluated by quantifying adherence
to protein-coated polystyrene and by measuring oxidant production,
detected by chemiluminescence after exposure to complement-opsonized
zymosan. CD18 was quantified cytofluorometrically. Plasma collected
at end ischemia and during early reperfusion effected no significant
alterations of adhesion, oxidant production or CD18. Late reperfusion
plasma (between 8 and 48 hours) significantly increased adherence and
oxidant production (to 4.11+/-0.61 and 2.60+/-0.32 times the values
of preischemic plasma, p<0.006). Peak adherence, oxidant
production and CD18 expression were evoked synchronously, by 24 hour
plasma. CD18 expression increased only at 24 hours and did not
increase proportional to increases in adherence and oxidant
production. Control plasma (nonischemic, n=5) elicited no significant
differences of any inflammatory measure during sham ischemia or
reperfusion. These results indicate that endogenous mediators may
evoke a progressive systemic inflammatory response after ischemia by
stimulating CD18-dependent neutrophil function in a delayed but
prolonged manner.
Received 12 August 1994; accepted in final form 28 September
1995.
APS Manuscript Number H727-4.
Article publication pending Am. J. Physiol. (Heart Circ. Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 6 November 95