The myeloperoxidase (MPO)-derived oxidant hypochlorous acid (HOCl/OCl(-)) is implicated in the pathogenesis of atherosclerosis and other inflammatory states. We have synthesized an imaging probe, sulfonaphthoaminophenyl fluorescein (SNAPF), that selectively reacts with HOCl. SNAPF detects HOCl produced by stimulated MPO-expressing cells cultured from human whole blood, as well as HOCl from bone marrow (BM)-derived macrophages isolated from transgenic mice that express human MPO. Two lines of evidence indicate that SNAPF permits the in vivo imaging of HOCl production. First, we used this approach to demonstrate HOCl production by neutrophils in experimental murine peritonitis. Second, we detected HOCl production by MPO expressing cells in human atherosclerotic arteries. Thus, fluorescence reflectance imaging by SNAPF may provide a valuable noninvasive molecular imaging tool for implicating HOCl and MPO in the damage of inflamed tissues.

Binding of highly branched poly(N-isopropylacrylamide) with vancomycin end groups to Staphylococcus aureus induced a coil-to-globule phase transition. The polymers aggregated this gram-positive bacteria (but not gram-negative bacteria) over a wide range of temperatures, but cooling to 24-26 degrees C progressed the polymer-bound bacteria through a globule-to-coil phase transition, after which the bacteria were released.

Interleukin-1 receptor antagonist-deficient (Il1rn-/-) BALB/c mice developed inflammation localized to the skin of the ear pinna in 64% of the cases examined. Histopathologically, the disease had many features resembling human psoriasis, suggesting that it might be a useful disease model. The epidermis became thickened and hypertrophic, and expressed the immature keratin, K6, throughout. The stratum corneum showed parakeratotsis. Large epidermal projections formed into a grossly thickened dermis and both tissues were infiltrated by leukocytes. Neutrophil-rich microabscesses formed beneath the stratum corneum. Dendritic cells and activated T cells of both helper classes were identified in both the dermis and epidermis, while a high density of macrophages was seen in the dermis, where mast cells were also prominent. Dense patterns of apparently activated small dermal vessels were seen in the diseased dermis. Cutaneous inflammation, along with arterial inflammation and arthritis, is the third site-specific, inflammatory disease to be found to affect Il1rn-/- BALB/c mice. None of the diseases affected Il1rn-/- C57BL/6. In F2 hybrids of Il1rn-/- BALB/c and C57BL/6, cutaneous inflammation was absent, aortic inflammation was common, and arthritis was rare, indicating that the sets of background modifier genes that cause susceptibility to each disease are not fully overlapping.