Nancy A. McNelly

Capillaries in aging rat olfactory bulb: A quantitative light and electron microscopic analysis

Olfactory bulbs from Charles River (Crl) rats from 3 to 36 months have been examined with light and electron microscopy. Total capillary length, surface, and volume, as well as number of endothelial cells, increases during the twofold increase in olfactory bulb volume from 3 to 18 months, but the relative density of these parameters shows no change during this time; from 18 to 36 months when neuronal cell body and dendrites are decreasing markedly in size, the relative density of capillaries shows only a modest decrease. Capillary lumen size and capillary wall thickness remain the same throughout life, but basal lamina thickness doubles from 3 to 24 months and then remains constant from 24 to 36 months. The incidence of several unusual ultrastructural features of the outer capillary basal lamina has been shown to increase with age.

Factors influencing fetal macrophage development: III. Immunocytochemical localization of cytokines and time‐resolved expression of differentiation markers in organ‐cultured rat lungs

Exogenous TNFα, IL‐1β, M‐CSF, and GM‐CSF all stimulate growth of macrophages arising in explanted fetal rat lungs. The present study examines the intrinsic availability of these factors in intact and organ‐cultured lungs and utilizes expression of cytokines and marker proteins to explore the differentiation pathway followed by phagocytes in vitro.

Variation in longevity of rats: Evidence for a systematic increase in lifespan over time

Male-Sprague-Dawley rats (CrL:CD(SD)BR) were maintained under barrier conditions at Charles River Breeding Laboratories (Wilmington MA) from August, 1975, to July, 1983. Animals were provided food and water ad libitum. Survival data from 8 completed cohorts of 100 animals each and one continuing cohort reveal a highly significant linear increase in median lifespan, yielding a 26% increase in this parameter for cohorts born over a period of less than six years. The biological factors responsible for this increase are not clear at present. Nevertheless, these results in outbred rats, taken in conjunction with previous observations of a trend towards increased longevity in inbred mice, indicate that the assumption of cohort equivalence underlying many cross-sectional studies of biological aging may not be valid.

Factors influencing fetal macrophage development: I. Reactions of the tumor necrosis factor-α cascade and their inhibitors

When fetal rat lungs are explanted to organ culture, precursor angular cells soon convert to nascent macrophages that multiply rapidly as they mature into efficient phagocytes. The present study examines the influence of proinflammatory early cytokines of the tumor necrosis factor‐alpha (TNFα) cascade on this initial expression of the macrophage phenotype.

Development of Cellular Host Defense Mechanisms

The lungs are well guarded against damage from inhaled gases, particulates, and microbes by a variety of local defenses provided by resident cells and hematological defenses provided by leukocytes and their products acting in the lungs. Various mechanisms are used in these defenses, and they come into being at different times during lung development as effector cells differentiate. In general, operation of all such defenses improves as cells become experienced in immunological cross talk or link up with sensory and motor nerves, and the time newly differentiated cells require to reach this state depends on cell type. Physiological processes of more macroscopic scale, represented by pulmonary mechanics and lung reflexes involving the central nervous system, eventually contribute substantially to these host defenses. Discussion of their ontogeny is beyond the scope of this review, which is limited to more intimate cellular interactions.

Factors influencing fetal macrophage development: II. Effects of the PDGF subfamily of protein-tyrosine kinase receptor ligands as studied in organ-cultured rat lungs

Macrophage precursors in pseudoglandular rat lungs rapidly differentiate into phagocytes in organ culture, although this occurs only gradually in vivo. Macrophage colony‐stimulating factor is vital for the process, but the possible importance of other ligands in the platelet‐derived growth factor (PDGF) subfamily is scarcely appreciated.