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ABSTRACT: Activation of mast cells in all organs in which this phenomenon has been studied leads to increased vascular permeability. Mucosal edema is thought to be an important component of the airflow obstruction of asthma. In order to develop a model to study IgE-mediated vascular permeability in lung, rats were passively sensitized with a murine monoclonal IgE-anti-dinitrophenyl (DNP). Forty-eight hours later, the animals were challenged intravenously with mouse serum albumin conjugated to DNP (1 to 25 micrograms) and received 125I-labeled bovine albumin at the same time to permit assessment of leakage of vascular proteins into the lungs. The animals became cyanotic, but they did not die. Control animals were challenged with mouse serum albumin alone and experienced no systemic reactions. The trachea, the hilum, and peripheral lung were removed and the radioactivity determined. Compared to control animals, vascular permeability was increased most impressively in the trachea and to a lesser extent in the hilum. No increased vascular permeability was found in the peripheral lung. In dose-response experiments (1 to 25 micrograms MSA-DNP injected), the peak effect in the trachea occurred at 25 micrograms MSA-DNP (+450 +/- 119% above control values, p less than or equal to 0.05), while the response in the bronchus was less dose dependent; maximal increase above control was at 12.5 micrograms DNP-MSA (+50 +/- 8%, p less than or equal to 0.05). The increased plasma exudation in the trachea and bronchi peaked within 5 min of antigen challenge and remained significantly increased for at least 2 h. After 8 h, no increased radioactivity could be observed.(ABSTRACT TRUNCATED AT 250 WORDS)
The American review of respiratory disease 12/1988; 138(5):1295-9. · 10.19 Impact Factor
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ABSTRACT: The interaction of substance P (SP) with specific receptors in intact lung tissue was autoradiographically visualized, using slide-mounted tissue sections of rat lung tissue. SP receptors are highly concentrated in the central airways and are not detectable in peripheral bronchi, vessels, and alveoli. Within central airways, receptor distribution is most concentrated in the epithelium and small vessels in the lamina propria. Smooth muscle in airway or blood vessel walls expressed no detectable SP receptors. Immunohistochemical staining for SP revealed SP-containing nerves in the same areas where the receptors are localized. Displacement curves of SP bound to rat lung indicated that the C-terminal fragment was much more effective than the N-terminal fragment at competing for SP binding. Injection of 0.3 to 30 nmol/kg SP dramatically increased vascular permeability in the trachea and to a lesser extent in the hilus. Peripheral lung failed to respond to SP with increased vascular permeability unless toxic concentrations of SP were employed. SP increased the transudation of protein into the trachea within 5 min of injection, and the extravasated protein persisted through at least 2 h. Both SP and SP(3-11) were capable of stimulating increased vascular permeability, but SP(1-4) was inactive. SP caused mast cell degranulation as reflected in increased plasma histamine levels after SP or SP(3-11) injection, but SP(1-4) had no effect. In order to determine if histamine release caused by SP contributed to the vascular permeability response, the effects of H1 and H2 antihistamine treatment were studied.(ABSTRACT TRUNCATED AT 250 WORDS)
The American review of respiratory disease 08/1988; 138(1):151-9. · 10.19 Impact Factor
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ABSTRACT: The binding sites for [125I]-vasoactive intestinal polypeptide (125I-VIP) in rat spleen and brain were localized using autoradiography. High affinity VIP receptors are present in rat spleen, and competition studies reflect structure-activity relationship typical of VIP receptors elsewhere. In spleen, specific binding of 125I-VIP occurs on red pulp and, most abundantly, on the periarteriolar lymphoid sheath (PALS) of white pulp. Unlabeled VIP competes for binding to both red pulp and white pulp, whereas secretin displaces binding to PALS more potently than to red pulp. This indicates that expression of VIP and/or secretin type receptors is limited to T lymphocytes of white pulp. In red pulp, VIP receptor bearing cells probably are monocytes/macrophages since this is the most abundant red pulp cell type. In the brain, VIP receptors are widely distributed with the highest densities occurring in "sensory" areas. Receptors are abundant in the olfactory bulb, thalamic nuclei, several cranial nuclei and the area postrema. High levels of 125I-VIP binding occurred on inner walls of blood vessels of the brain and spleen. The distribution patterns of receptors for "VIP-ergic signals" in brain and lymphoid tissue indicate interrelatedness of the two organ systems. This may serve as one biochemical rationale for a bio-psycho-social view of health and disease.
Peptides 02/1988; 9 Suppl 1:21-8. · 2.43 Impact Factor
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ABSTRACT: Substance P receptors were investigated in rat esophagus using 125I-Bolton-Hunter substance P as a labeling probe. Autoradiographic studies show that esophageal submucosa contains clusters of high-affinity substance P binding sites [maximum binding (Bmax) 4.2 +/- 0.28 fmol/mg protein; dissociation constant (Kd) 0.1 +/- 0.01 X 10(9) M]. The receptor distribution pattern is typical for submucous neurons. These data suggest that substance P may act as a neurotransmitter in rat esophagus.
The American journal of physiology 08/1987; 253(1 Pt 2):R167-71.
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ABSTRACT: A significant number of asthmatic subjects are provoked by allergic reactions. The underlying pathophysiologic event is mast cell degranulation with the release and generation of the mediators of anaphylaxis. Histamine, one of the major mast cell mediators, causes 10- to 50-fold increases in guinea pig lung cyclic 3',5'-guanosine monophosphate (cyclic GMP) through H1 receptor stimulation. Employing monoclonal antibodies directed at cyclic GMP, immunocytochemical techniques were used to identify those specific cells in lung responding to histamine stimulation with increases in cyclic GMP. The most responsive cells were alveolar and parenchymal macrophages, pleural lining cells, and endothelial and epithelial cells. Little or no increases in bronchial or vascular smooth muscle cyclic GMP was noted. At the height of the reaction, a generalized increase in cyclic GMP staining of all alveolar cells was observed. These findings suggest that the lining cells of the lung including macrophages, mesothelial, endothelial, and epithelial cells may be the most responsive cells to histamine released during allergic responses. The absence of muscular staining suggests that cyclic GMP does not participate in histamine-stimulated muscle contraction.
The American review of respiratory disease 03/1987; 135(2):456-62. · 10.19 Impact Factor
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Annals of the New York Academy of Sciences 02/1987; 496:205-10. · 3.15 Impact Factor
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ABSTRACT: Bombesin found in neuroepithelial bodies and oat cell carcinoma of the lung, is thought to play an important role in normally developing and malignant lung. Monocytes-macrophages and human small cell lung carcinoma cells share several features, including macrophage-specific surface markers and the expression of functional receptors for bombesin-like neuropeptides and growth factors. Because small cell lung carcinoma cells synthesize immunoreactive bombesin, we investigated the possibility that alveolar macrophages also contain bombesin, a plausible hypothesis considering the many reports of neuropeptide production by immune cells and cells of bone marrow origin. Adherent human peripheral blood mononuclear cells as well as human and guinea pig alveolar macrophages were found to contain bombesin. The peptide was detected by radioimmunoassay, immunohistochemistry, high-pressure liquid chromatography with the use of different monospecific antibodies.
The Journal of Immunology 01/1987; 137(12):3928-32. · 5.79 Impact Factor
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ABSTRACT: The interaction of substance P with intact lymphatic tissue was quantified and autoradiographically visualized, using slide-mounted tissue sections of rat spleen. Radiolabeled substance P binds rapidly to an apparently single class of noninteracting high affinity sites (Kd = 2.4 nmol/L; Bmax = 9.4 fmol/mg protein). The ligand selectivity pattern suggests that substance P binding sites are similar to substance P receptors found in other tissues, including the brain, T lymphocytes, and macrophages. Substance P receptors are highly concentrated in the antigen-trapping spleen marginal zone, with low densities being found in the red pulp. No specific binding of radiolabel to T cell-dependent immunologic domains of the spleen is seen. The distribution of substance P receptors suggests that substance P is probably involved in the control of sensory functions of the immune system.
Blood 01/1987; 68(6):1398-401. · 9.90 Impact Factor
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ABSTRACT: In this study, we identified a population of dendritic cells (DC) that exists throughout human and mouse pulmonary tissues, including the trachea, bronchi, alveoli, and visceral pleura. In human tissue, these DC were shown to be positive for HLA-DR and T200 antigens. In the mouse, the DC expressed not only Ia and the T200 antigen, but also Fc-IgG and C3bi receptors. Unlike alveolar macrophages, the DC were negative for nonspecific esterase staining and shared ultrastructural similarities with the DC described by Steinman (1), and with Langerhans' cells, even though they did not contain Birbeck granules. We were able to demonstrate that mouse pulmonary DC function in antigen presentation, as observed with the other DC. Thus, the respiratory tract contains DC that are capable of functioning in antigen presentation and that may be important in pulmonary immune responses.
Journal of Experimental Medicine 03/1986; 163(2):436-51. · 13.85 Impact Factor
