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Polymorphonuclear leukocyte integrins in chronic renal failure
Gregorio Caimi1, Maria Montana, Caterina Carollo
1Dipartimento di Medicina Interna, Malattie Cardiovascolari e Nefrourologiche, Università di Palermo, Palermo, Italy. caimigre@unipa.it
Clinical Hemorheology and Microcirculation
|January 25, 2005
Summary
Patients with chronic renal failure (CRF) exhibit altered white blood cell (leukocyte) adhesion molecule patterns. This may contribute to their increased cardiovascular risk, suggesting new therapeutic targets for cardiovascular disease in CRF.
Area of Science:
- Nephrology
- Immunology
- Cardiovascular Medicine
Background:
- Chronic renal failure (CRF) patients face higher cardiovascular mortality than the general population.
- Traditional risk factors do not fully account for this increased cardiovascular risk.
- Leukocytes are hypothesized to play a role in CRF-associated cardiovascular complications.
Purpose of the Study:
- To investigate the beta2-integrin expression pattern on polymorphonuclear leukocytes (PMN) in patients with mild CRF.
- To compare PMN beta2-integrin expression in CRF patients versus healthy controls, both at baseline and after in vitro activation.
Main Methods:
- Flow cytometry was used to analyze the expression of PMN beta2-integrin adhesion molecules (CD11a, CD11b, CD11c, CD18).
- In vitro activation of PMNs was performed using 4-phorbol-12-myristate-13-acetate (PMA) and N-formyl-methionyl-leucyl-phenylalanine (fMLP).
- Indirect immunofluorescence was employed for phenotypical expression analysis.
Main Results:
- CRF patients showed increased baseline expression of CD11b, CD11c, and CD18 on PMNs compared to controls.
- In normal subjects, activation increased all measured adhesion molecules.
- In CRF patients, activation increased CD11b, CD11c, and CD18, but not CD11a expression.
Conclusions:
- Mild CRF is associated with an altered PMN beta2-integrin pattern.
- This altered pattern suggests a state of PMN activation in CRF patients.
- The findings may have pathophysiological significance for the high incidence of cardiovascular events in CRF.