Decreased Response of Human Milk Leukocytes to Chemoattractant Peptides

Abstract

ABSTRACT. To test the hypothesis that neutrophils and macrophages in human milk may not defend by classical inflammatory mechanisms, experiments were conducted to ascertain whether adherence, orientation, and directed motility of these leukocytes would be enhanced by exposure to chemoattractant peptides including N-formyl-L-methionyl-L-phenylalanine and N-formyl-L-methionyl-L-leucyl-L-phenylalanine and C5a generated from zymosan activated human serum. Adherence and spatial orientation were tested on coverglasses and in Zigmond chambers, and chemotaxis was examined by Boyden chambers and a subagarose technique. Whereas, the adherence, orientation, and directed movement of adult peripheral blood neutrophils and monocytes were significantly enhanced by those chemotactic agents, human milk leukocytes failed to respond. The failure of the response of human milk leukocytes was not due to alterations in maternal peripheral blood leukocytes but appeared to be due partially to inhibitors in human milk. The experiments suggest that human milk leukocytes may be modified in the mammary gland to protect by noninflammatory mechanisms. There is considerable evidence that breast-fed infants, particularly in underdeveloped countries, are protected against gastrointestinal pathogens (for review, see References 1-3). The manner in which this protection occurs is not known despite a host of descriptive studies of the immunologic system in human milk. Epidemiologic investigations suggest, however, that the protection may not depend upon the induction of inflammation by host resistance factors in human milk. For example, when infants from rural Central America received human milk natu-

Activated and memory T lymphocytes in human milk

“…Recent studies indicated that certain functions of HM neutrophils and macrophages are altered compared to their counterparts in human peripheral blood (PB). The adherence, orientation, and directed movement of HM neutrophils and macrophages were significantly less than those of PB neutrophils and monocytes after stimulation with chemoattractants such as N-formylmethionyl peptides and C5a [48]. In contrast, in vitro experiments utilizing a type 1 collagen gel assay demonstrated that the spontaneous motility of HM macrophages was much greater than that of PB mononuclear cells [331.…”

Chemokinetic Agents for Monocytes in Human Milk: Possible Role of Tumor Necrosis Factor-α

“…Furthermore, the adher-collagen was precipitated by the addition of an equal volume of ence and directed movement of human milk macrophages are 20% (w/v) NaC1. The precipitate was pelleted by centrifugation not increased by chemoattractant agents (12). This suggested that at 3000 X g for 1 h, washed, and resuspended in 3% acetic acid special populations of blood monocytes may be attracted to the to achieve a final concentration of 1.2 mg/ml.…”

“…Additional experimental observations supported those possibilities. In contrast to the lack of movement of neutrophils in human milk (12)(13)(14), it was discovered that HMM spontaneously moved more rapidly than blood monocytes in a three-dimensional, type I collagen matrix (1 5).In this study, the genesis of the increased motility of human milk macrophages was investigated. We tested whether circulating systemic factors produced early in lactation, mammary gland tissue factors, or constituents in human milk up-regulated the motility of blood monocytes.…”

“…Additional experimental observations supported those possibilities. In contrast to the lack of movement of neutrophils in human milk (12)(13)(14), it was discovered that HMM spontaneously moved more rapidly than blood monocytes in a three-dimensional, type I collagen matrix (1 5).…”

Future Research in Human Milk

“…The phagocytes may be able to generate toxic oxygen radicals, but they are not upregulated by chemoattractant agents (50). Furthermore, the neutrophils d o not move well in vitro (50,51), whereas the macrophages migrate readily into three-dimensional matrices (5 1). Perhaps, the two classes of ~haaocvtes in human milk have a dichotomy of function.…”