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Increased Anionic Peptide Distribution and Intensity during Progression and Resolution of Bacterial Pneumonia

Amanda J. Fales-Williams,¹ Jack M. Gallup,¹ Rafael Ramírez-Romero,^1, Kim A. Brogden,² and Mark R. Ackermann^1*

Department of Veterinary Pathology, College of Veterinary Medicine, Iowa State University, Ames, Iowa 50011-1250,¹ Respiratory Diseases of Livestock Research Unit, National Animal Disease Center, Agricultural Research Service, U.S. Department of Agriculture, Ames, Iowa 50010²

Received 6 June 2001/ Returned for modification 14 August 2001/ Accepted 3 October 2001

Anionic peptides (APs) are small anionic antimicrobial peptides composed of 7 aspartic acid residues and are produced in the lungs of humans, sheep, and cattle. Although expression by epithelial cells of some antimicrobial peptides (e.g., ß-defensins) of humans and ruminants is increased in response to acute infection, AP expression is not increased during acute infection, which suggests that the expression of the latter peptide is constitutive. In this study, the degree of AP expression during the progression (acute, subacute, and chronic) of bronchopneumonia was determined. Mannheimia (Pasteurella) haemolytica, a known inducer of bovineß-defensins, was inoculated intrabronchially with a fiber-optic bronchoscope in nine 3-month-old sheep, and tissues were collected at 1, 15, and 45 days postinoculation (p.i.); nine control animals received pyrogen-free saline by the same procedure and were killed at the same time points. In the acute group (1 day p.i.), the lungs had lesions typical of bronchopneumonia and the distribution and intensity of AP immunoreactivity (AP-IR) were similar to those of previous studies (minimal intensity and distribution of AP-IR in bronchiolar epithelial cells). In the subacute group (15 days p.i.), there was prominent hyperplasia of bronchiolar and alveolar epithelial cells, and the chronic group (45 days p.i.) had yet more pronounced hyperplasia. In the subacute and chronic groups, the intensity and distribution of AP-IR in the cytoplasm of hyperplastic bronchiolar and type II alveolar cells were significantly increased compared to those of saline-inoculated and contralateral (noninoculated) lung lobes. Although AP expression appears constitutive, the constitutive production of AP is higher in hyperplastic, less differentiated cells than in fully differentiated, mature cells of the respiratory airways. The increased intensity and distribution of AP-IR in immature (hyperplastic) epithelial cells may be a mechanism by which production of a noninducible antimicrobial is increased temporarily during lesion progression and repair. This increased production of AP by hyperplastic cells may protect the lung against further infection until new, fully differentiated epithelial cells are capable of expressing their own inducible array of antimicrobial peptides.

Present address: Departamento de Patología, Facultad de Medicina Veterinaria y Zootecnia, Universidad Autónoma de Nuevo León, Monterrey, N.L., México.

This article has been cited by other articles:

• Fales-Williams, A. J., Brogden, K. A., Huffman, E., Gallup, J. M., Ackermann, M. R. (2002). Cellular Distribution of Anionic Antimicrobial Peptide in Normal Lung and during Acute Pulmonary Inflammation. Vet Pathol 39: 706-711 [Abstract] [Full Text]