title: Mechanisms of systemic vasodilation by lysozyme-c in septic shock.
abstract: In septic shock (SS), cardiovascular collapse is caused by the release of inflammatory mediators. We previously found that lysozyme-c (Lzm-S), released from leukocytes, contributed to systemic vasodilation in a canine model of SS. We then delineated the pathway by which this occurs in a canine carotid artery organ bath preparation (CAP). We showed that Lzm-S could intrinsically generate hydrogen peroxide (H(2)O(2)) and that H(2)O(2) subsequently reacted with endogenous catalase to form compound I, an oxidized form of catalase. In turn, compound I led to an increase in cyclic guanosine 3',5'-monophosphate to produce vasodilation. However, it was not clear from previous studies whether it is necessary for Lzm-S to bind to the vasculature to cause vasodilation or, alternatively, whether the generation of H(2)O(2) by Lzm-S in the surrounding medium is all that is required. We examined this question in the present study in which we used multiple preparations. In a partitioned CAP, we found that when we added Lzm-S to a partitioned space in which a semipermeable membrane prevented diffusion of Lzm-S to the carotid artery tissue, vasodilation still occurred because of diffusion of H(2)O(2). On the other hand, we found that Lzm-S could accumulate within the vascular smooth muscle layer (VSML) after 7 h of SS in a canine model. We also determined that when Lzm-S was located in close proximity to vascular smooth muscle cells, it could generate H(2)O(2) to produce lengthening in a human cell culture preparation. We conclude that there are two mechanisms by which Lzm-S can cause vasodilation in SS. In one instance, H(2)O(2) generated by Lzm-S in plasma diffuses to the VSML to cause vasodilation. In a second mechanism, Lzm-S directly binds to the VSML, where it generates H(2)O(2) to produce vasodilation.
authors.affiliation: Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico.
authors.forename: Jose
authors.initials: J
authors.lastname: Gotes
authors.forename: Krika
authors.initials: K
authors.lastname: Kasian
authors.forename: Hans
authors.initials: H
authors.lastname: Jacobs
authors.forename: Zhao-Qin
authors.initials: ZQ
authors.lastname: Cheng
authors.forename: Steven N
authors.initials: SN
authors.lastname: Mink
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D004285:Dogs; D005707:Gallic Acid / Q000031:analogs & derivatives; D006801:Humans; D066298:In Vitro Techniques; D009113:Muramidase / Q000502:physiology*; D032389:Myocytes, Smooth Muscle / Q000502:physiology*; D012772:Shock, Septic / Q000503:physiopathology*; D014664:Vasodilation
chemical_list: C048734:ethyl gallate; D005707:Gallic Acid; D009113:Muramidase; C514728:lysozyme C, human