Monoamine oxidases (MAO; EC 1.4.3.4.) A and B occur in the outer mitochondrial membrane and oxidize a number of important biogenic and xenobiotic amines. Monoclonal antibodies specific for human MAO A or B and immunocytochemical techniques were used to visualize the respective enzymes in human placenta, platelets, lymphocytes, liver, brain, and a human hepatoma cell line. MAO A was observed in the syncytiotrophoblast layer of term placenta, liver, and a subset of neurons in brain, but was not observed in platelets or lymphocytes, which are known to lack type A enzyme. MAO B was observed in platelets, lymphocytes, and liver, but not in placenta, which contains little or no MAO B. MAO B was also observed in a subset of neurons in the brain that was distinct from that which contained MAO A. MAO A and MAO B were also observed in some glia. Unlike most tissues examined, liver cells appeared to contain both forms of the enzyme. These studies show that MAO A and MAO B can be specifically visualized by immunocytochemical means in a variety of human cells and tissues and can provide a graphic demonstration of the high degree of cell specificity of expression of the two forms of the enzyme.

Splenic lymphocytes and accessory cells express receptors for nerve growth factor (NGF), a well-characterized neurotropic peptide that influences the development and survival of neuronal elements in the central and peripheral nervous systems. In the present study, we report that when rat splenic mononuclear cells (MC) are incubated in the presence of NGF, a dose-dependent increase in DNA synthesis occurs during 96-120 hours of culture as measured by 3H thymidine (3H-Thd) uptake. The minimal molar concentration of NGF at which the increased proliferative response of the cells (3.7 nM) is seen corresponded to the equilibrium disassociation binding constant of the MC (Kd = 2.5 nM), suggesting that the response was a consequence of receptor-ligand interaction. In addition, NGF was able to potentiate the lymphoproliferative response to several T-cell and B-cell mitogens. Significantly increased 3H-Thd uptake by NGF-stimulated cells was noted for concanavalin A (Con A), phytohemagglutinin (PHA), and lipopolysaccharide (LPS), particularly at suboptimal dosages of mitogen. Thus it appears that the NGF receptors on rat splenic MC are physiologically relevant and that NGF can modulate proliferation of T- and B- cells.

An hypothesis was developed which predicts that human milk protects against infections of the alimentary tract of the breast-fed infant by non-inflammatory mechanisms. Human milk is poor in the initiators and mediators of inflammation and rich in anti-inflammatory agents. Furthermore, many of the anti-inflammatory agents are comparatively resistant to digestive enzymes and therefore might be expected to remain active in the gastrointestinal tract of the recipient. Further studies of these factors in in vivo models will be required to validate the hypothesis.

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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-

Considerable evidence is mounting to support the concept of a modulatory role for the brain and neuroendocrine system on the immune response. This neuroimmunomodulation occurs in part through the interaction of specific neurosubstances with receptors on lymphocytes and monocytes. Nerve growth factor (NGF) is a neuronotrophic factor necessary for the development and maintenance of sympathetic and embryonic sensory neurons. This trophic effect is initiated through binding of NGF at specific cell surface receptor sites on NGF-responsive cells. Several recent studies suggest that NGF may interact with cells of the immune system and may play a role in the regulation of some immunologic reactions. In this study we report on the presence of specific receptors for NGF on the surface of mononuclear cells from rat spleens. The NGF-binding sites are of the low-affinity type with Kd's in the 10(-9) M range. These receptors migrate on SDS-PAGE as two molecular species of approximately 190 and 125 kilodaltons. Our findings of receptors for NGF on lymphocytes and accessory cells support other evidence that NGF may influence immunoreactivity in vivo.

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The regulation of neuronal cell death by the neuronotrophic factor, nerve growth factor (NGF), has been described during neural development and following injury to the nervous system. Also, reduced NGF activity has been reported for the aged NGF-responsive neurons of the sympathetic nervous system and cholinergic regions of the central nervous system (CNS) in aged rodents and man. Although there is some knowledge of the molecular structure of the NGF and its receptor, less is known as to the mechanism of action of NGF. Here, a possible role for NGF in the regulation of oxidant--antioxidant balance is discussed as part of a molecular explanation for the known effects of NGF on neuronal survival during development, after injury, and in the aged CNS.