Figure 4.

Growth and survival‐promoting secretory leukocyte protease inhibitor (SLPI) activity may be mediated in part through progranulin (PRGN). (A) Protection of PRGN from elastase‐mediated loss. (B) Elastase causes apoptosis that is abrogated by wild type (WT)/SLPI and protease‐inhibitor null (PI‐) mutants. Cell cycle measures of G₁‐phase (top) and S phase (middle) were done in transfectants treated for 24 h with increasing concentrations of human neutrophil elastase (hNE) in serum‐free conditions. Those at 48 h measure percent of cells in subG₀G₁, (bottom) and demonstrate progressive loss of apoptosis in WT/SLPI and the PI‐/SLPI mutants (representative of n = 2). (C, D) Reduction of poly‐(ADP‐ribose) polymerase (PARP) (C) and caspase‐3 (D) cleavage in response to neutrophil elastase in WT/SLPI and PI‐ mutants (n = 2). Floating and adherent cells were collected for all analyses. F‐SLPI, PI‐/SLPI mutant Leu72Phe; R‐SLPI, PI‐/SLPI mutant Leu72Arg.