Document Type

Dissertation - University Access Only

Award Date

2003

Degree Name

Doctor of Philosophy (PhD)

Department / School

Biology and Microbiology

First Advisor

Alan J. Young

Abstract

Recent evidence suggests that components other than maternal immunoglobulins in colostrum may also have important roles in protection and in immune system development of neonates for both short- and long-term health. Cellular components of colostrum have been demonstrated to cross the intestinal wall, traffic into the peripheral blood, and enter secondary lymphoid and non-lymphoid tissues in the neonate. A large fraction of these colostral cells are macrophages that express membrane-bound CD14 and release two forms of soluble CD14 (sCD14). We proposed to: (1) examine colostral macrophages as a source of sCD14 to the neonatal calf, and (2) determine the effect of a recombinant bovine CD14 (rbCD14) on the maturation of peripheral blood monocytes and their capacity to function as phagocytic cells. A protocol was developed to isolate colostral mononuclear celis. Freshly isolated or cultured colostral mononuclear cells were monitored for expression of the antigen presenting cell (APC) markers MHC class I and class II, the inflammatory markers CDl la, b, c, and CD14, and the B cell markers IgG and IgM; for release of soluble CD14 to the culture medium; and for cell growth over the culture period. A second protocol was developed to separate monocytes from peripheral blood mononuclear cells of neonate or adult cattle. Neonatal or adult monocytes were then monitored before and after culture in the presence or absence of native sCD14 or rbCD14 for changes in (1) phenotypic expression of MHC class I and class II, CD 11 b and c, and CD 14, and (2) in functional capacity of phagocytic activity. The results indicated that fresh colostral mononuclear cells (macrophages) are activated, and that these cells released sCD14 and decreased CDl lb, CDl lc and mCD14 expression over 48 hours in culture. This sCD14 was biologically active, causing altered expression of surface IgG and IgM, proliferation of B cells, and differentiation of APCs. Treatment with rbCD 14 increased the proportion of neonatal monocytes expressing CDl lb. This induction of CDl lb expression combined with a lack of rbCD14- stimulated phagocytic activity indicated that sCD14 stimulates polarized differentiation of neonatal calf monocytes toward the dendritic cell phenotype. This suggests that colostral macrophages traffic into the neonatal circulation to release sCD 14 that stimulates polarized monocyte differentiation into dendritic cells. We surmise that colostral macrophages release sCD14 to neonatal tissues as a role in development of competent antigen-presenting cells required for a nai've T cell response.

Library of Congress Subject Headings

Calves -- Immunology.
Colostrum.
Maternally acquired immunity.
Macrophages.

Publisher

South Dakota State University

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Rights Statement

In Copyright