Patterns of changes in neutrophil adhesion molecules during normothermic cardiopulmonary bypass. A clinical study.
The adhesion of activated neutrophils to endothelial cells is a key feature of the inflammatory response to cardiopulmonary bypass (CPB) because it "unlocks" a cascade of cytotoxic events. This adhesion is made possibly by the sequential involvement of two sets of neutrophil cell surface receptors: L-selection and beta 2 integrins (CD 11 a/CD 18; CD 11 b/CD 18; CD 11 c/CD 18). We have assessed the changes in the expression of these adhesion molecules in ten patients who underwent various open-heart procedures with the use of "warm" (33.4 degrees-37 degrees C) CPB. Arterial blood samples were obtained before, during and after bypass and processed for immunofluorescent flow cytometric analysis. CD 11 a expression remained unchanged throughout the study period. Conversely, CD 11 b drastically increased early after the onset of bypass (at 15 min on bypass: 172 +/- 17 [mean fluorescence (arbitrary units), mean +/- SEM] versus 63 +/- 13 before bypass. P < 0.02) and was still markedly elevated 30 min after the end of bypass (160 +/- 38, P < 0.05 versus the pre-by-pass value). CD 11 c expression underwent a similar upregulation (at 15 min of bypass: 54 +/- 5 versus 34 +/- 5 at baseline, P < 0.01). L-selectin expression did not change significantly during the period of observation. Put together, these results suggest that CPB is associated with an increased adhesive potential of neutrophils, which enhances their binding to the vascular endothelium and thereby initiates tissue damage through the release of cytotoxic mediators from adherent cells. Manipulation of integrin expression could therefore represent an effective means of alleviating the component of bypass-induced inflammatory tissue damage which is more specifically neutrophil-mediated.
Le Deist
F
F
INSERM U-132, Hôpital Necker-Enfants Malades, Paris, France.
Menasché
P
P
Bel
A
A
Larivière
J
J
Piwnica
A
A
Bloch
G
G
D000328:Adult; D000368:Aged; D002315:Cardiopulmonary Bypass / Q000379:methods; D002318:Cardiovascular Diseases / Q000601:surgery; D015815:Cell Adhesion Molecules / Q000378:metabolism; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D019041:L-Selectin / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009504:Neutrophils / Q000378:metabolism*; D011379:Prognosis; D016024:Receptors, Cytoadhesin / Q000378:metabolism*; D013696:Temperature
D015815:Cell Adhesion Molecules; D016024:Receptors, Cytoadhesin; D019041:L-Selectin