New insights into the role of Plg-RKT in macrophage recruitment.

Plasminogen (PLG) is the zymogen of plasmin, the major enzyme that degrades fibrin clots. In addition to its binding and activation on fibrin clots, PLG also specifically interacts with cell surfaces where it is more efficiently activated by PLG activators, compared with the reaction in solution. This results in association of the broad-spectrum proteolytic activity of plasmin with cell surfaces that functions to promote cell migration.

The plasminogen receptor, Plg-R(KT), and macrophage function.

When plasminogen binds to cells its activation to plasmin is markedly enhanced compared to the reaction in solution. Thus, cells become armed with the broad spectrum proteolytic activity of plasmin. Cell-surface plasmin plays a key role in macrophage recruitment during the inflammatory response.

Regulation of macrophage migration by a novel plasminogen receptor Plg-R KT.

Localization of plasmin on macrophages and activation of pro-MMP-9 play key roles in macrophage recruitment in the inflammatory response. These functions are promoted by plasminogen receptors exposing C-terminal basic residues on the macrophage surface. Recently, we identified a novel transmembrane plasminogen receptor, Plg-R(KT), which exposes a C-terminal lysine on the cell surface.

Spantide I decreases type I cytokines, enhances IL-10, and reduces corneal perforation in susceptible mice after Pseudomonas aeruginosa infection.

Purpose: To determine the effects of blocking substance P (SP) interactions with its major receptor (NK1-R) using the antagonist spantide I in susceptible mice infected with Pseudomonas aeruginosa.

Methods: Immunohistochemistry and enzyme immunosorbent assay (EIA) tested levels of SP in the cornea of B6 and BALB/c mice. B6 mice were treated with spantide, and after infection, slit lamp examination; clinical score; bacterial counts; and myeloperoxidase (MPO), RT-PCR, ELISA, and polymorphonuclear (PMN) cell chemotaxis assays were performed.

Vasoactive intestinal peptide balances pro- and anti-inflammatory cytokines in the Pseudomonas aeruginosa-infected cornea and protects against corneal perforation.

Corneal infection with Pseudomonas aeruginosa perforates the cornea in susceptible C57BL/6 (B6), but not resistant BALB/c, mice. To determine whether vasoactive intestinal peptide (VIP) played a role in development of the resistant response, protein expression levels were tested by immunocytochemistry and enzyme immunoassay in BALB/c and B6 corneas. Both mouse strains showed constitutive expression of corneal VIP protein and nerve fiber distribution.

IFN-gamma: regulation of nitric oxide in the P. aeruginosa-infected cornea.

Purpose: BALB/c mice are resistant to Pseudomonas aeruginosa (P. aeruginosa) keratitis and bacterial killing/stasis requires nitric oxide (NO). NO regulation in the cornea is unknown and was tested in this model.

Matrix metalloproteinase-9 amplifies the immune response to Pseudomonas aeruginosa corneal infection.

Purpose: The purpose of this study was to determine the role of matrix metalloproteinases (MMP) in Pseudomonas aeruginosa keratitis.

Methods: Gene array and selective real-time PCR examined MMP expression in the cornea of susceptible (C57BL/6, B6) versus resistant (BALB/c) mice before and after infection; zymography tested enzyme activity for MMP-2 and -9. Clinical score, Langerhans cell (LC), and Neutrophil (PMN) quantitation were done in recombinant (r) MMP-9, antibody neutralized, and MMP-9(-/-) mice.

Substance P regulates natural killer cell interferon-gamma production and resistance to Pseudomonas aeruginosa infection.

Studies have shown that after Pseudomonas aeruginosa (P. aeruginosa) corneal infection, BALB/c mice that are capable of resolving the disease, locally produce IFN-gamma. As T cells are not detected in the infected cornea of these mice, antibody depletion was used to test whether NK cells produce the cytokine.

Role of IL-12 and IFN-gamma in Pseudomonas aeruginosa corneal infection.

Purpose: In Pseudomonas aeruginosa ocular infection, T-helper cell 1-responsive mouse strains are susceptible (the cornea perforates), and neutralization of IFN-gamma before infection has been shown to delay the onset of perforation. IFN-gamma is the predominant cytokine induced by IL-12, and positive regulation of IL-12 by IFN-gamma, if unchecked, leads to excessive cytokine production and toxicity. Despite its potential importance, the role of IL-12 in ocular infection with P.