BRIEF REPORT |
Correspondence to: Daniel S. Friend, Div. of Rheumatology and Immunology, Smith Building, Rm. 628, One Jimmy Fund Way, Boston, MA 02115.
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Summary |
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Acid aspiration causes pulmonary vascular permeability and PMN sequestration. By increasing pulmonary mast cells through adoptive transfer of v-abl-transformed mast cells (V3MCs) into BALB/c mice, we now show that the greater mast cell number in the lung is associated with increased pulmonary injury. (J Histochem Cytochem 49:793794, 2001)
Key Words: alveolitis, mast cells, polymorphonuclear cells, vascular permeability
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Introduction |
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Acid aspiration-induced acute alveolitis is mediated by several cellular and humoral factors (
One million v-abl-transformed mast cells (V3MCs) were injected IV into 68-week-old male BALB/c mice (Taconic Farms; Germantown, NY). Previous studies (
Results (mean ± SEM) were analyzed after subtraction of sham value by one-way ANOVA and the Bonferroni procedure for multiple comparisons. Acid aspiration led to lung injury in the BALB/c mice, PI 0.023 ± 0.0025 compared to the saline sham control animals, PI of 0.008 ± 0.0015 (n=3, p<0.05). Acid-injured V3MC mice showed a marked increment in lung PI to 0.090 ± 0.0046 (n=5, p<0.05) in comparison with the saline sham V3MC mice, PI 0.037 ± 0.005 (n=4, p<0.05). A fourfold augmentation of the PI was observed in the V3MC acid-injured mice relative to the acid-injured BALB/c mice (n=4, p<0.05).
The bronchoalveolar lavage PMN counts in the V3MC animals (1218 ± 165) that underwent acid injury was threefold higher relative to the acid-injured BALB/c animals (403 ± 85) and 30-fold compared to the saline-aspirated V3MC mice (40 ± 4) (n=3, p<0.05). Histological grading confirmed the lung injury in accordance with the PI and the BAL neutrophil quantification. Histologic analysis revealed that by Day 14 after injection, large numbers of the granulated mast cells populated the lung in the V3MC-injected mice (Fig 1b). They appeared principally in the alveolar septae. As assessed immunohistochemically, the V3MCs expressed the chymases mMCP-1 and mMCP-2 in their granules. After acid aspiration, some of the mast cells in both the V3MC and BALB/c mice were degranulated and mMCP-1, but not mMCP-2, was found to coat the surface of the surrounding alveolar macrophages in the acid- aspirated lungs (Fig 2a). Macrophages in the bronchoalveolar lavage of acid-injured mice also were coated with the chymase mMCP-1 (Fig 2b) but not mMCP-2.
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We utilized a novel model of mastocytosis to define a direct role for mast cells in the pulmonary inflammatory response in acid aspiration injury and also to implicate mast cell protease mMCP-1 as functioning at the alveolar macrophage plasma membrane.
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Footnotes |
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Presented in part at the Joint Meeting of the Histochemical Society and the International Society for Analytical and Molecular Morphology, Santa Fe, NM, February 27, 2001.
Received for publication December 7, 2000; accepted February 16, 2001.
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Literature Cited |
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