Induction of lung emphysema is prevented by L-arginine-threonine-arginine.

In patients with chronic obstructive pulmonary disease (COPD), an inflammatory process is ongoing in the lungs, with concomitant damage of the alveolar structures and loss of airway function. In this inflammatory process, extracellular matrix degradation is observed. During this lung matrix degradation, small peptide fragments consisting of proline and glycine repeats generated from collagen fibers are liberated from the matrix by matrix metalloproteinases. Chemotactic activities of these collagen-derived peptides such as N-acetyl-proline-glycine-proline (PGP) via CXCR1 and CXCR2 have been reported. We show here that PGP induces neutrophil migration in vivo, which is dose dependent. Moreover, PGP is involved in the development of emphysema-like changes in the airways. The complementary peptide, L-arginine-threonine-arginine (RTR), has been shown to bind to PGP sequences and inhibit neutrophil infiltration. We show that RTR impedes both PGP- and interleukin-8-induced chemotaxis in vitro. In vivo, RTR prevents both migration and activation of neutrophils induced by PGP. Furthermore, RTR completely inhibits PGP-induced lung emphysema, assessed by changes in alveolar enlargement and right ventricular hypertrophy. In conclusion, these data indicate that collagen breakdown products, especially PGP, are important in the pathogenesis of COPD and that PGP antagonism via RTR ameliorates lung emphysema.

Conceptual development of the immune system as a sixth sense.

Understanding how and why the immune and nervous systems communicate in a bidirectional pathway has been fundamental to the development of the psychoneuroimmunology (PNI) field. This review will discuss some of the pivotal results that found the nervous and immune systems use a common chemical language for intra and inter-system communication. Specifically the nervous and immune systems produce a common set of peptide and nonpeptide neurotransmitters and cytokines that provides a common repertoire of receptors and ligands between the two systems. These studies led to the concept that through the sharing of ligands and receptors the immune system could serve as a sixth sense to detect things the body cannot otherwise hear, see, smell, taste or touch. Pathogens, tumors, and allergens are detected with great sensitivity and specificity by the immune system. As a sixth sense the immune system is a means to signal and mobilize the body to respond to these types of challenges. The paper will also review in a chronological manner some of the PNI-related studies important to validating the sixth sense concept. Finally, the review will suggest ways to apply the new found knowledge of the sixth sense to understanding a placebo effect and developing new therapeutic approaches for treatment of human diseases.