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

Abstract

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., ␤-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 bovine ␤-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.

Antimicrobial peptides and surfactant proteins in ruminant respiratory tract disease

“…During acute M. haemolytica infection of calves, anionic peptide expression was not increased suggesting constitutive expression (Fales-Williams et al, 2002a). A similar study in sheep suggested anionic peptide was increased only during chronic M. haemolytica pneumonia the source of the anionic peptide was reparative hyperplastic epithelium (Fales-Williams et al, 2002b). Efforts to assess activity against M. haemolytica bacteria showed within minutes of inoculation anionic peptide bound to the bacteria causing degenerative ultrastructural changes suggesting bacteriocidal effects (Heidari et al, 2002).…”

“…These peptides are expressed constitutively and mediate antimicrobial activity against Gram-negative and Gram-positive bacteria (Fales-Williams et al, 2002b;Brogden et al, 1996Brogden et al, , 1997.…”

Field‐Driven Biofunctionalization of Polymer Fiber Surfaces during Electrospinning

“…The PEO-peptide conjugate is sufficiently short to facilitate diffusion [42] through solvated PEO during electrospinning, whereas the PEO segment of the conjugate is still long enough to i) permit co-crystallization with the PEO matrix to anchor the oligopeptide along the fiber surface, and ii) possibly function as a spacer between the fiber surface and the biofunctional peptide segment. While the anionic oligopeptide sequence in (SEE) 3 -PEO may exhibit antimicrobial activity [43] (which is beyond the scope of this work), it is expected to alter solution properties before, as well as respond to the applied electric field during, electrospinning. Solution viscosities measured at different (SEE) 3 -PEO concentrations (relative to PEO) in aqueous PEO solutions reveal two trends: i) an increase in PEO concentration promotes an increase in viscosity, and ii) an increase in (SEE) 3 -PEO content at fixed PEO Figure 1.…”

Collectins and Cationic Antimicrobial Peptides of the Respiratory Epithelia

“…71,150 Anionic peptides are small, hydrophilic peptides that contain homopolymeric regions (e.g., 5-7 residues) of aspartic acid, which are responsible for their negative charge. 16,41 They have been detected in the lungs, bronchoalveolar lavage (BAL) fluid, and pulmonary surfactant of humans, sheep, and cattle. For maximal bactericidal activity, APs require zinc as a cofactor, which may allow the peptide to overcome the net negative charge once on the microbial surface.…”