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Nutritional Immunology

Intrauterine Undernutrition in Rats Interferes with Leukocyte Migration, Decreasing Adhesion Molecule Expression in Leukocytes and Endothelial Cells¹

Laboratory of Hypertension and Inflammation, Department of Pharmacology, Institute of Biomedical Sciences, University of São Paulo, Brazil and ^* Department of Medicine, School of Medical Sciences, University of Santiago, Chile

²To whom correspondence should be addressed. E-mail: zbfortes{at}icb.usp.br.

Experimental and epidemiologic data have shown that malnutrition predisposes individuals to infections. Immune responses are compromised, particularly in undernourished children. Therefore, we investigated the migratory capacity of leukocytes, using the intravital microscopy technique, in male Wistar rats (8–9 wk of age) that were undernourished in utero after their dams were fed 50% less food than the amount consumed by control dams. The number of leukocytes rolling along the venular endothelium, sticking after stimulation with leukotriene B₄, tumor necrosis factor- (TNF-) or zymosan-activated plasma, or migrating after TNF- stimulation was significantly reduced in the undernourished rat offspring. Compared with nourished rat offspring, undernourished offspring had significantly reduced numbers of circulating leukocytes, higher blood pressure, and higher leukocyte rolling velocity (V_WBC), as well as a higher ratio between V_WBC and RBC velocity (V_RBC). Endothelial P-selectin and intercellular adhesion molecule-1 (ICAM-1) expression, analyzed by immunohistochemistry, and basal leukocyte L-selectin expression, analyzed by flow cytometry, were significantly reduced in the undernourished rat offspring. Because the groups did not differ in leukocyte CD11/18 expression, endothelial expression of platelet-endothelial cell adhesion molecule-1, or venular blood flow velocity and, consequently, venular shear rate, we conclude that intrauterine undernutrition in rats reduces leukocyte migration, downregulates endothelial expression of P-selectin and ICAM-1, as well as leukocyte expression of L-selectin, while reducing leukocyte counts. The higher V_WBC and V_WBC/V_RBC ratio may also play a role in this reduced leukocyte migration. Our data suggest that this phenomenon is involved in the increased predisposition to infections in undernourished subjects.

KEY WORDS: • intrauterine malnutrition • leukocyte migration • adhesion molecules

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